Metabolite Profiling of 5'-AMP-Induced Hypometabolism.
Metabolite Profiling of 5'-AMP-Induced Hypometabolism.
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DOI：
10.1007/s11306-013-0552-7
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发表时间：
2014-02-01
期刊：
影响因子：
3.6
通讯作者：
Lee, Cheng Chi
中科院分区：
文献类型：
--
作者：
Zhao, Zhaoyang;Van Oort, Anita;Tao, Zhenyin;O'Brien, William G., III;Lee, Cheng Chi
我们已经证明，5′-腺苷一磷酸（5′-AMP）可用于诱导小鼠和其他非冬眠哺乳动物的深度代谢低下。这种可逆的5′-AMP诱导的低基质血症（AIHM）允许小鼠在自发逆转为低温之前保持体温高于环境温度约1°C数小时。我们的生物化学和基因表达研究表明，AIHM行为中涉及的分子过程最有可能发生在代谢互变水平，而不是基因或蛋白质表达水平。为了了解AIHM行为中涉及的代谢过程，我们在经历AIHM的动物的血浆、肝脏和大脑中的AIHM的多个阶段进行了非靶向比较代谢组学研究。使用结合LC-MS和GC-MS的代谢物分析平台检测和测量了代表许多重要代谢途径的数十种代谢物。我们的研究结果表明，有一个广泛的抑制能量产生的代谢途径，但脂质代谢似乎是最低限度的改变。碳水化合物代谢物的调节似乎是动物在AIHM和随后的恢复过程中利用能量的主要方式。当动物进入AIHM时，给药的5′-AMP大部分已被分解代谢。在AIHM期间，尿素循环似乎是功能性的，有助于避免氨毒性。在所有研究的组织中，大脑的代谢物通量受AIHM的影响最小。
We have demonstrated that 5′-adenosine-monophosphate (5′-AMP) can be used to induce deep hypometabolism in mice and other non-hibernating mammals. This reversible 5′-AMP induced hypomatabolism (AIHM) allows mice to maintain a body temperature about 1°C above the ambient temperature for several hours before spontaneous reversal to euthermia. Our biochemical and gene expression studies suggested that the molecular processes involved in AIHM behavior most likely occur at the metabolic interconversion level, rather than the gene or protein expression level. To understand the metabolic processes involved in AIHM behavior, we conducted a non-targeted comparative metabolomics investigation at multiple stages of AIHM in the plasma, liver and brain of animals that underwent AIHM. Dozens of metabolites representing many important metabolic pathways were detected and measured using a metabolite profiling platform combining both LC–MS and GC–MS. Our findings indicate that there is a widespread suppression of energy generating metabolic pathways but lipid metabolism appears to be minimally altered. Regulation of carbohydrate metabolites appears to be the major way the animal utilizes energy in AIHM and during the following recovery process. The 5′-AMP administered has largely been catabolized by the time the animals have entered AIHM. During AIHM, the urea cycle appears to be functional, helping to avoid ammonia toxicity. Of all tissues studied, brain’s metabolite flux is the least affected by AIHM.
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影响因子：
4.6
作者：
Epperson, L. Elaine;Karimpour-Fard, Anis;Martin, Sandra L.
通讯作者：
Martin, Sandra L.
影响因子：
4.6
作者：
Nelson, Clark J.;Otis, Jessica P.;Carey, Hannah V.
通讯作者：
Carey, Hannah V.
DOI：
10.1073/pnas.78.11.6858
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
AMES, BN;CATHCART, R;HOCHSTEIN, P
通讯作者：
HOCHSTEIN, P
影响因子：
4.8
作者：
Daniels, Isadora Susan;Zhang, Jianfa;Lee, Cheng Chi
通讯作者：
Lee, Cheng Chi
DOI：
10.1152/ajpregu.00888.2006
发表时间：
2007-07-01
影响因子：
2.8
作者：
Swoap, Steven J.;Rathvon, Meaghan;Gutilla, Margaret
通讯作者：
Gutilla, Margaret